Mutation analysis of 77 patients with normal-karyotype myelodysplastic syndrome
10.3760/cma.j.issn.1003-9406.2019.09.001
- VernacularTitle: 正常核型骨髓增生异常综合征患者的基因变异谱系分析
- Author:
Wei QIN
1
;
Meiyu CHEN
;
Xiaohui CAI
;
Hongying CHAO
;
Jie LIU
;
Naike JIANG
;
Min ZHOU
;
Xuzhang LU
;
Suning CHEN
;
Ri ZHANG
;
Chuan HE
;
Qian WANG
Author Information
1. Department of Hematology, the Affiliated Changzhou Second Hospital of Nanjing Medical University, Changzhou, Jiangsu 213003, China; Jiangsu Provincial Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of the Ministry of Health, the First Affiliated Hospital of Suzhou University, Suzhou, Jiangsu 215006, China
- Publication Type:Journal Article
- Keywords:
Myelodysplastic syndromes;
Gene landscape;
Normal karyotype
- From:
Chinese Journal of Medical Genetics
2019;36(9):857-861
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To carry out mutation analysis for patients with myelodysplastic syndromes (MDS) and a normal karyotype.
Methods:Targeted capture and next-generation sequencing (NGS) was carried out using a customized 49-gene panel. FLT3 internal tandem duplication (FLT3-ITD), CALR, NPM1 and CEBPA mutations were detected by PCR and Sanger sequencing.
Results:Sixty two patients (80.5%) were found to harbor at least one mutation. Each patient has carried 2.21 mutations in average. Coexistence of ≥ 3 mutations was common (43.7%). The most commonly mutated genes were RUNX1 (23.4%, 18/77), ASXL1 (18.2%, 14/77), NPM1 (15.6%, 12/77), U2AF1 (15.6%, 12/77), DNMT3A (11.7%, 9/77). Patients with SF3B1 mutations were significantly older than those with ASXL1 mutations (P=0.023). Mutations of the DNMT3A gene were significantly associated with the blood platelet level compared with BCOR mutations (P=0.02). No significant difference was found in the number and rate of mutations between those under or above 60-year-old. Among 67 patients with clinical follow-up, 20 (29.8%) has transformed to acute myeloid leukemia, and the time of transformation has ranged from 1 to 44 months, with a average of 5.3 months. RUNX1, U2AF1 and FLT3 mutations are associated with leukemic transformation.
Conclusion:Coexistence of ≥ 3 mutations are frequent among patients with normal-karyotype MDS. Certain mutations are associated with age and leukemic transformation.
